Browsing by Author "Gomes, Bruno Costa"
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- Aplicação da biomonitorização humana para avaliação da exposição ocupacional a hidrocarbonetos aromáticos policíclicos na Europa: uma revisão da literaturaPublication . Louro, Henriqueta; Gomes, Bruno Costa; Saber, Anne Thoustrup; Iamiceli, Anna Laura; Göen, Thomas; Jones, Kate; Katsonouri, Andromachi; Neophytou, Christiana; Vogel, Ulla; Ventura, Célia; Oberemm, Axel; Duca, Radu Corneliu; Fernandez, Mariana F.; Olea, Nicolas; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoOs hidrocarbonetos aromáticos policíclicos (HAPs) são produtos químicos com impacto em saúde ocupacional, pelo que a avaliação da exposição humana através de estudos de biomonitorização tem aumentado nos últimos anos. No entanto, os dados obtidos são ainda insuficientes para os reguladores e decisores políticos. Este trabalho, no contexto da Iniciativa Europeia em Biomonitorização Humana (HBM4EU), descreve uma revisão da literatura sobre a exposição ocupacional aos HAPs na Europa, entre 2008 e 2022, com o objetivo de identificar as vantagens e limitações dos vários biomarcadores de exposição e /ou de efeito, bem como o conhecimento em falta para melhorar a regulamentação. Os resultados da análise dos 42 artigos elegíveis para inclusão nesta revisão demonstram que o biomarcador de exposição mais utilizado é o 1-hidroxipireno urinário, sendo os biomarcadores de efeito mais comuns, biomarcadores de stresse oxidativo e genotoxicidade. Globalmente, verificou-se a necessidade de desenvolver novas abordagens de recolha de dados e amostras, bem como a seleção apropriada de biomarcadores de forma a obter dados fiáveis e comparáveis em diferentes setores industriais. Além disso, a aplicação de biomarcadores de efeito contribui para a identificação de ambientes de trabalho ou atividades de alto risco, possibilitando medidas de mitigação e gestão de risco.
- A case study on occupational exposure to Chromium (VI), Nickel, PAH mixtures and lung cancer.Publication . Silva, Maria João; Louro, Henriqueta; Viegas, Susana; Gomes, Bruno Costa; Santonen, Tiina; Kortenkamp, Andreas; Lebret, ErikBackground: In several industries, e.g., aircrafts maintenance, workers are co-exposed to a range of hazardous substances, including hexavalent chromium [Cr (VI)], nickel (Ni) and polycyclic aromatic hydrocarbons (PAHs). Each of these compounds can cause serious health effects, including lung cancer. However, the association between exposure and health outcome has not been analysed from a mixture perspective, i.e., considering the potential interactive effects of those substances as determinants of lung cancer. Here we present the development of a case study on occupational exposure to Cr (VI), Ni and PAHs to advance the identification of mixture health effects and to progress towards a more refined risk assessment. Methods: A tiered framework is applied that includes a first step of collection of relevant hazard (e.g., genotoxicity) and exposure information gathered from literature or from HBM4EU databases on occupational cohorts. Then, this information will be used to construct hazard quotients derived from relevant occupational exposure limits for Cr (VI), Ni and PAHs, followed by the determination of the Hazard Index (HI). Results: The estimations based on available literature search will be presented and discussed, keeping the perspective of its contribution to generate directions for the exposure, hazard, and risk assessments. In addition, the biomonitoring levels of Cr (VI) and Ni and the data on external levels of PAHs produced in the chromate occupational exposure study, will allow a refinement of the exposure assessment, comparatively to the literature-based results obtained. Conclusions: It is anticipated that the assessment of the risk from occupational co-exposure to Cr(VI), Ni and PAHs - based on data obtained from a EU-wide harmonised study - will add on building a framework for mixtures risk assessment, that can be further applied for substances to which co-exposure occurs or/and are expected to produce similar health outcomes.
- HBM4EU chromates study: the Portuguese integrated and harmonized study on exposure to hexavalent chromium and related early effects.Publication . Viegas, Susana; Martins, Carla; Ribeiro, Edna; Ladeira, Carina; Pinhal, Hermínia; Nogueira, Ana; Santos, Sílvia; Tavares, Ana; Gomes, Bruno Costa; Afonso, Catarina Maia; Louro, Henriqueta; Silva, Maria JoaoIn the scope of the European Union (EU) human biomonitoring initiative, a multicentric study on different occupational settings from several European countries was performed, to provide information on occupational exposure to hexavalent chromium [Cr(VI)], a known lung carcinogen. Biomonitoring approaches were used to obtain exposure data to support the implementation of new risk management measures and policy actions at the national and European levels. This work describes the Portuguese contribution to the study, which aimed to assess workers' exposure to Cr, by using exposure biomarkers (urinary chromium [U-Cr]), and industrial hygiene samples (air and hand wipes) and to link exposure to potential long-term health effects by using effect biomarkers. Exposure determinants influencing exposure were explored from the contextual information and human biomonitoring data. The ultimate goal of the study was to appraise the risk management measures contributing to minimize exposure and protect workers' health. Several occupational settings and activities were considered, including plating, welding, and painting. A control group from the Portuguese general population was also included. Data on age, sex, and smoking habits from both groups were considered in the statistical analysis. Information on the risk management measures available for workers was collected and used to identify the ones that mainly contributed to reduce exposure. Environmental monitoring and human biomonitoring revealed that painters were the highest exposed group. The use of respiratory protection equipment showed an influence on total U-Cr levels for workers involved in painting activities. Concerning early health effects, the painters presented also a significantly higher level of DNA and chromosomal damage in peripheral blood cells, as compared to the control group, suggesting a plausible association between exposure to Cr(VI) and early genotoxic effects. The results showed that workers are exposed to Cr(VI) in those occupational settings. These findings point to the need to improve the prevention and risk management measures and the implementation and enforcement of new regulatory actions at the national level.
- Occupational exposure to Hexavalent chromium: the portuguese case within the collaborative european human biological monitoring studyPublication . Afonso, Catarina; Gomes, Bruno Costa; Louro, Henriqueta; Ladeira, Carina; Pinhal, Hermínia; Nogueira, Ana; Santos, Sílvia; Ventura, Célia; Ribeiro, Edna; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoBackground: The EU human biomonitoring initiative (HBM4EU) aims to coordinate and advance human biomonitoring across Europe. A multicenter study intending to characterize occupational exposure to hexavalent chromium [Cr(VI)], a human carcinogen, was setup in several industrial settings across Europe. In Portugal, the study was developed in one aircraft maintenance company since the substitution of Cr(VI) in this sector is not expected in the near future. Methods: The work processes that could imply exposure to Cr(VI) were characterized and exposure estimation was done. Following the company agreement and the volunteers informed consent, a survey was applied to each worker for detailed information on lifestyle, health status, etc.. Sampling for exposure and effect biomarkers analyses involved industrial hygiene samples (HIS) and biological specimens from 50 workers and 25 non-exposed individuals (controls). Biomarkers of early biological effects were studied in leukocytes from all individuals, involving the analysis of DNA damage (comet assay) and chromosome alterations (micronucleus assays); the results obtained for exposed and control individuals were statistically compared. Results and Discussion: Besides HIS results, Cr (VI) concentrations in biological samples and effect biomarkers results will be presented. The complementarity of the environmental and biological sampling, together with the sensitivity and specificity of the biomarkers used, is expected to allow exposure characterization and possible early genotoxic effects identification. Potential associations between exposure and effect biomarkers will be explored. Conclusions: An association between the levels of exposure to Cr(VI) and the early effects characterized in workers, if existent, is expected to predict potential health outcomes for Cr(VI)-exposed workers, particularly, on the long-term. All the information generated will help to support new priorities and investments regarding risk management measures to apply in this company and in the aircraft maintenance sector, in general.
- Occupational exposure to hexavalent chromium: biomarkers of genotoxicity in human peripheral bloodPublication . Afonso, Catarina; Gomes, Bruno Costa; Louro, Henriqueta; Nogueira, Ana; Pinhal, Hermínia; Reis, Susana; Ventura, Célia; Ladeira, Carina; Ribeiro, Edna; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoThe hexavalent chromium [Cr(VI)] is a human carcinogen, which is still authorized for use in several industrial settings because it has been difficult to replace. This was the reasoning to select it as a priority chemical by the European Human Biomonitoring Initiative (HBM4EU, https://www.hbm4eu.eu/), which aims to bridge chemicals human exposure to their possible impact on health. For that purpose, not only exposure needs to be assessed but also early effect biomarkers are valuable to reflect health outcomes. The cytokinesis-block micronucleus (CBMN) assay in peripheral blood lymphocytes (PBLs) is one of the most widely used effect biomarker for measuring chromosome alterations in human cells. Since it represents a measure of both chromosome breakage and loss, an increased frequency of micronucleated cells (MNC) can reflect the effect from exposure to genotoxic agents. Moreover, there is evidence that the micronucleus (MN) frequency in PBLs is predictive of cancer risk. As part of an European multi-centre occupational study, 50 Portuguese workers exposed on a daily basis to Cr(VI) and 27 healthy controls non-exposed to Cr(VI) or other chemicals were studied. The present work intended to assess, in a more detailed manner, the early effects in a subgroup of workers (n=6) that use daily paints with Cr(VI), comparatively to that of a control group matched for age, gender and smoking habits. All participants accepted to participate by signing an informed consent previously to the blood withdrawal. An individual questionnaire to collect contextual information, e.g. personal information, lifestyle habits (smoking habits, alcohol consumption, diet), and health status was filled. Personal air samples were collected in order to assess occupational exposure to Cr(VI) soluble and insoluble compounds. Following blood culture, lymphocytes harvesting and staining using standardized methods, MNC were scored in 2000 PBL per individual. The frequencies of MNC obtained for the exposed and control groups were compared using Fisher’s exact test. Results from personal air sampling are still under evaluation. A significantly increased frequency of MNC was observed in PBLs of the 6 workers under study, comparatively to the matched controls (p < 0.001, Fisher’s exact test). These results are in line with the preliminary data obtained for the overall exposed group vs controls. The present results suggest that the frequency of micronuclei in PBLs is a reliable early effect biomarker in the case of occupational exposure to Cr(VI). Moreover, the findings also suggest a potential health risk for this group of workers. These results should promote the investment in new risk management measures and the effective application of the ones already in place, such as adequate local exhaust ventilation and a more frequent use of personal protective equipment. Additional work, considering the overall exposed group, will be developed aiming to clarify if the obtained results are due to the single exposure to Cr(VI) or to the co-exposure to several other chemicals commonly present in this type of occupational setting.
- Plan for development of case studies - Deliverable Report AD 15.1 WP 15 - Mixtures, HBM and human health riskPublication . Kortemkamp, Andreas; Mengelers, Marcel; Vinggaard, Anne Marie; Silva, Maria João; Slamay, Remy; Vermeulen, Roel; Vlaanderen, Jelle; Ottenbros, Ilse; Viegas, Susana; Gomes, Bruno Costa; Louro, Henriqueta; Lebret, ErikThis deliverable describes the activities in task 15.3 leading up to the development of cases studies for mixture health effects and outlines the proposed case studies. The proposed case studies are: · Developmental neurotoxicity beyond polybrominated diphenylethers · Heavy metals and nephrotoxicity · Anti-androgenic chemicals and male reproductive health · Chromium (VI), nickel and polycyclic aromatic hydrocarbons and lung cancer · Addressing exposure misclassification in mixture studies The Addendum provides further details about multi-year perspective and timing, as well as detailed budgetary aspects per case study.
- The use of effect biomarkers in human biomonitoring studies: exposure to hexavalent chromiumPublication . Gomes, Bruno Costa; Louro, Henriqueta; Huuskonen, Pasi; Santonen, Tiina; Huumonen, Katriina; Ndaw, Sophie; Fernández, Mariana F.; Silva, Maria JoãoHexavalent chromium, Cr(VI) is a human carcinogen (Group 1, IARC), and its expo-sure has been associated with increased lung cancer risk, particularly in exposed workers. The general population may be exposed to Cr(VI) through food, drinking water and tobacco smoke. Under the Human Biomonitoring for Europe Initiative (HBM4EU), Cr(VI) has been considered a priority substance, indicating the need for generating and analyzing data on human exposure and effects, both as single sub-stance and in mixtures. Although many epidemiological studies have reported data on human exposure to Cr(VI), comparably fewer included effect biomarkers assess-ment. However, these biomarkers are central to identify early biological effects be-fore the onset of any adverse health effect. Additionally, biomarkers provide a link between human exposure and health outcomes, when considered in an adverse outcome pathway (AOP) perspective. In this work, we present the results of a critical review on the conventional and po-tentially new biomarkers for Cr(VI) early biological effects, which may be linked to adverse health outcomes in humans. The results show that the most frequently analyzed effect biomarkers concerning Cr(VI) exposure have been those associated with oxidative stress and genotoxicity (comet and micronucleus in blood cells). Urinary 8-isoprostane, a marker of lipid pe-roxidation, has also been used to relate Cr(VI) exposure to lung cancer. More recent-ly, single-gene alterations as well as omics-based biomarkers e.g., genomic or epigenomic changes and protein signatures, have been pointed as novel effect bi-omarkers, but they still need to be further developed and validated. In the literature revision, the most important knowledge gaps have also been identi-fied and discussed, such as the need of additional mechanistic data, in the perspec-tive of building an AOP for Cr(VI) occupational exposure and lung cancer
- The Use of Human Biomonitoring to Assess Occupational Exposure to PAHs in Europe: A Comprehensive ReviewPublication . Louro, Henriqueta; Gomes, Bruno Costa; Saber, Anne Thoustrup; Iamiceli, Anna Laura; Göen, Thomas; Jones, Kate; Katsonouri, Andromachi; Neophytou, Christiana M.; Vogel, Ulla; Ventura, Célia; Oberemm, Axel; Duca, Radu Corneliu; Fernandez, Mariana F.; Olea, Nicolas; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoPolycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers’ health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008–2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.
- The Usefulness of Early Effect Biomarkers in Monitoring Occupational Exposure to Hexavalent ChromiumPublication . Afonso, Catarina; Gomes, Bruno Costa; Louro, Henriqueta; Nogueira, Ana; Pinhal, Hermínia; Reis, S.; Ventura, Célia; Ladeira, Carina; Ribeiro, Edna; Santonen, Tiina; Viegas, Susana; Silva, Maria JoãoIntroduction: In the frame of the Project HBM4EU (https://www.hbm4eu.eu/) a biomonitoring study is being conducted across Europe to characterize occupational exposure to hexavalent chromium [Cr(VI)], a recognized human lung carcinogen. Herein we present the results of biomarkers of exposure and effect characterized in a group of workers from a Portuguese aircraft maintenance company, where Cr(VI) replacement is not expected in the near future. Methods: All participants signed an informed consent and responded to a questionnaire to collect contextual information. Cr(VI) exposure was assessed by the analysis of personal air samples; total Cr was measured in urine and blood samples from 50 workers and 26 controls. The effects biomarkers included the alkaline comet assay and the cytokinesis-block micronucleus assay in blood in leukocytes. Results: The concentrations of Cr in the air samples were variable, depending on the activities performed. Noteworthy, workers engaged in painting exterior surfaces with Cr(VI)-reach paints were exposed to the highest Cr(VI) levels. Results from biomonitoring confirmed the occurrence of internal exposure. Furthermore, significantly increased micronuclei frequencies (p < 0.001, Fisher’s exact test) and DNA damage levels were identified in leukocytes from workers comparatively to controls. Interestingly, among the painters showed up a group of 6 workers who were exposed to a mixture of Cr, organic solvents, silica, and other chemicals and who displayed an elevated level of micronucleated cells comparatively to matched controls. Conclusions: An association between Cr(VI) exposure and genotoxicity biomarkers was found, raising concern about a potentially increased cancer risk. Furthermore, these results suggest that the effect biomarkers selected are useful to strengthen the exposure data, in that more exposed or vulnerable groups can be more reliably detected. This is relevant to allow the prioritization of occupational hygiene and risk management measures implementation in the workplace.
- Using human biomonitoring for the risk assessment of polycyclic aromatic hydrocarbons in occupational exposuresPublication . Viegas, Susana; Gomes, Bruno Costa; Louro, Henriqueta; Silva, Maria João; Joksić, Agnes Šömen; Kirinčič, Stanislava; Mahiout, Selma; Santonen, TiinaBackground and Purpose: The Human Biomonitoring Initiative (HBM4EU) is a joint effort of 28 countries, the European Environment Agency and the European Commission, co-funded under Horizon 2020. HBM4EU is generating evidence of the current exposure of European citizens to chemicals and the possible health effects in order to assess the associated risks and support policy making towards human health protection. Polycyclic aromatic hydrocarbons (PAH) were considered one of the 1st priority substance groups to be addressed. In the scope of this project, the present work aimed to evaluate the added value of human biomonitoring (HBM) for the PAH risk assessment process, in the case of occupational exposure. Methods: An extensive literature search was performed to identify scientific papers published between 2008 and 2018 that included air monitoring and HBM data in several occupational settings based in Europe. Among them, those papers presenting urinary 1-hydroxypyrene (1-OHP) quantification - the most common exposure biomarker of pyrene and a surrogate for exposure to PAHs mixtures - were selected. Based on the 1-OHP values the excess lifetime cancer risk (ELCR) for workers, concerning lung cancer, was estimated following the ECHA recent approach (https://echa.europa.eu/fi/applying-for-authorisation/evaluating-applications). ELCR values calculated using air and HBM data were compared. Results: Based on the criteria described, only 7 out of 28 papers were considered for ELCR estimation. Overall, high ELCR values were estimated (several values higher than 10-4). Moreover, for some studies (3 out of 7) the ELCR estimation using HBM data yielded values higher than those estimated from air monitoring data. This might indicate that, for those specific workplaces, transdermal absorption or even hand-mouth exposure can have an important role in the total exposure to PAH and that the HBM data allows a more accurate PAH exposure assessment. Nevertheless, these findings should be interpreted with caution, since ELCR estimates from air monitoring data are based on Benzo[a]pyrene (BaP) concentrations while HBM-based ELCR determination uses urinary 1-OHP concentration that reflects exposure not only to BaP but to all PAHs, irrespectively of sources or routes of exposure. This work claims attention for two main aspects, namely: i) the exposure levels are still high in some occupational settings and ii) there is a need for developing new occupational studies, applying a set of exposure biomarkers or a more specific biomarker for BaP exposure, which would allow a better ELCR estimation for exposed workers.